The studies proposed here are designed to elucidate the molecular bases for the intrinsic modulation(s) of the activities of a presumptive "salvage" pathway enzyme, TdR kinase or its isozymes and the physiological significance of such regulatory change(s) in the maintenance of the intracellular deoxythymidylate pools in diverse human tissues. Comparative studies of the activities of TdR kinase and TdR phosphorylase, the enzyme competing for TdR, will be carried out in a wide spectrum of normal proliferating, differentiated and malignant tissues and in fibroblsts from normal subjects and individuals with a genetic predisposition to cancer. These studies will provide adequate background as well as the proper perspectives for evaluating the regulation of kinase activity. Antigenic properties, isozyme profiles as well as standard biochemical and physico-chemical parameters will be used to characterize the two enzymes. Studies assessing the contribution of mucin, substrates and other intracellular metabolites to the aggregation-disaggregation phenomenon in human colonic mucosa and term placenta can lend insight into regulation in vivo and perhaps, even into cellular localization of the enzyme. Antigenicity and biochemical parameters such as heat lability, isozyme pattern and response to mercaptans will be assessed along with kinase-like activity in plasma for potential diagnostic value in the detection of premalignant changes or recurrence of malignancy after treatment. BIBLIOGRAPHIC REFERENCES: Salser, J.S., Ball, Jr., W.J., and Balis, M.E. Biochemical changes in premalignant intestines. Cancer Research 36, 3495-3498, 1976. Ball, Jr., W.J., Salser, J.S., and Balis, M.E. Biochemical changes in preneoplastic rodent intestines. Cancer Research 36, 2686-2689, 1976.